Synthesis and rearrangement of benzopirano[4,3-c]pirazole derivatives

Article abstract of DOI:10.1070/MC2005v015n02ABEH001942

Benzopirano[4,3-c]pirazole derivatives have been synthesised, and their intramolecular disproportionation and stereochemical features have been discussed.

Full text of DOI:10.1070/MC2005v015n02ABEH001942

, 2005, 15(2), 83–84
Synthesis and rearrangement of benzopirano[4,3-c]pirazole derivatives
Roman V. Rudenko, Sergey M. Desenko, Valentin A. Chebanov,* Vitaly N. Chernenko and Vladimir I. Musatov
Scientific and Technological Corporation ‘Institute for Single Crystals’, Institute for Scintillation Materials,
National Academy of Sciences of Ukraine, 61001 Kharkov, Ukraine. E-mail: chebanov@isc.kharkov.com
DOI: 10.1070/MC2005v015n02ABEH001942
Benzopirano[4,3-c]pirazole derivatives have been synthesised, and their intramolecular disproportionation and stereochemical
features have been discussed.
Benzopyrano[4,3-c]pyrazole derivatives 2a–d were synthesised
by condensation of arylidenechromanones 1a–d with hydrazine
(Scheme 1). The structures of these compounds were studied by
peaks of aromatic protons and, in the case of 2b, a singlet of the
methoxy group.
Compounds 2a–d contain two chiral centres in the 3- and
3a-positions. Published data suggest a possibility of forming
both cis and trans isomers in the reactions of arylidenechro-
manones 1a–d with hydrazine.1–3 However, the 1H NMR spectra
1
1H NMR spectroscopy.† The H NMR spectra of benzopyrano-
[4,3-c]pyrazoles 2a–d contain signals of protons in the 3-, 3a-
and 4-positions of the heterocycle with appropriate multiplicity,
Mendeleev Commun. 2005 83

, 2005, 15(2), 83–84
NH
N
O
1 N
5 O
R
2NH
O
O
3
KOH/DMSO/DMF
R
N2H4
R
3a
H
H
4
NH
OH
N
2a–c
1a–d
2a–d
R
a R = H
b R = MeO
c R = Cl
a R = H
b R = MeO
c R = Cl
d R = NO2
Me
3a–c
Scheme 1
Scheme 2
of 2a–d do not contain signs of doubling the signals. It points to
the formation of only one of possible diastereomers. Analysis
of spin–spin coupling constants of the CH–CH–CH2 fragment
of the heterocycle and NOE data allow us to fix a relational
configuration of substituents in 2a–d: the values of J3aH–3H
(13.3–14.3 Hz) are more typical of axial–axial coupling con-
stants. The NOE experiment shows a spatial nearness of protons
in the 3-, 3a- and 4-positions. Analysis of the geometry of
compound 2a obtained from quantum chemical calculations
(GAMESS,4 HF 6-31G**) indicates that protons at the 3- and
3a-positions are able to give NOE in both cis and trans orienta-
tions, but 3H and a proton in the 4-position can reveal NOE
only in the case of trans orientation of 3 and 3a. Thus, com-
pounds 2a–d were obtained as trans isomers containing aryl
substituents in equatorial positions.
The molecules of compounds 2a–d contain partially hydro-
genated pyran and pyrazoline rings. It was established that the
refluxing of 2a–c in a mixture of DMSO and DMF in the pres-
ence of KOH leads to rearrangement with pyran ring opening,
and the oxidation of a pyrazoline fragment gave pyrazoles 3a–c
(Scheme 2). Under the same conditions, compound 2d decayed
and no product was isolated from the reaction mixture.
In the 1H NMR spectra of 3a–c,‡ the signals of the CH–CH–
CH2 fragment of pyranopyrazoline bicycle disappeared but peaks
attributed to protons of methyl and hydroxyl groups appeared.
References
1 A. Levai, A. Szolljsy and G. Toth, J. Chem. Res. (S), 1985, 392.
2 A. Levai, J. Heterocycl. Chem., 1998, 35, 13.
3 N. Sangwan and S. Rastogi, Indian J. Chem., 1981, 20B, 135.
4 M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S. Gordon,
J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. J. Su, T. L. Windus,
M. Dupuis and J. A. Montgomery, J. Comput. Chem., 1993, 14, 1347.
†
A solution of arylidenechromanone 1a (0.005 mol, 1.18 g) and
hydrazine hydrate 99% (0.008 mol, 0.4 ml) in 15 ml of MeOH was
boiled for 30 min. After cooling, the precipitate was filtered off and
crystallised from methanol; 64% of product 2a was obtained. Com-
pounds 2b, 2c and 2d in 68, 74 and 75% yields, respectively, were
synthesised in a similar manner.
Received: 20th May 2004; Com. 04/2267
1
2a: mp 132 °C. H NMR (200 MHz, [2H6]DMSO) d: 3.38 (ddd, 1H,
‡
3a-H, J 12.3, 6.0 and 13.8 Hz), 4.20 (dd, 1H, 4-HA, J –11.2 and 12.3 Hz),
4.56 (dd, 1H, 4-HB, J –11.2 and 5.9 Hz), 4.66 (d, 1H, 3-H, J 13.6 Hz),
6.9–7.7 (m, 9H, ArH).
Compound 2a (0.002 mol, 0.5 g) was dissolved in a mixture of 5 ml
DMF and 1 ml DMSO and 0.1 g KOH was added. The mixture was
boiled for 3 h, poured into water and neutralised with a 10% HCl
solution. The product was filtered off and crystallised from EtOH; 30%
of pyrazole 3a was obtained. Compounds 3b and 3c in 42 and 35%
yields, respectively, were synthesised in a similar manner.
3a: mp 142 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 2.17 (s, 3H,
Me), 6.9–7.7 (m, 9H, ArH), 10.4 (br. s, 1H, OH). MS, m/z (%): 250 (75),
146 (100), 55 (30).
1
2b: mp 137 °C. H NMR (200 MHz, [2H6]DMSO) d: 3.42 (ddd, 1H,
3a-H, J 12.4, 6.1 and 13.8 Hz), 3.74 (s, 3H, OMe), 4.18 (dd, 1H, 4-HA,
J –11.6 and 10.7 Hz), 4.51 (dd, 1H, 4-HB, J –11.7 and 6.1 Hz), 4.58 (d,
1H, 3-H, J 13.8 Hz), 6.8–7.7 (m, 8H, ArH).
1
2c: mp 152 °C. H NMR (200 MHz, [2H6]DMSO) d: 3.40 (ddd, 1H,
3a-H, J 12.4, 6.3 and 14.3 Hz), 4.20 (dd, 1H, 4-HA, J –11.3 and 10.4 Hz),
4.55 (dd, 1H, 4-HB, J –11.4 and 5.8 Hz), 4.66 (d, 1H, 3-H, J 14.3 Hz),
6.85–7.7 (m, 8H, ArH).
3b: mp 126 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 2.19 (s, 3H,
Me), 3.82 (s, 3H, OMe), 6.9–7.6 (m, 8H, ArH), 10.3 (br. s, 1H, OH).
MS, m/z (%): 280 (65), 146 (100), 55 (32), 73 (20), 60 (18).
3c: mp 186 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 2.15 (s, 3H,
Me), 6.9–7.8 (m, 8H, ArH), 10.4 (br. s, 1H, OH). MS, m/z (%): 284 (86),
146 (100), 130 (66), 43 (34).
1
2d: mp 214 °C. H NMR (200 MHz, [2H6]DMSO) d: 3.43 (ddd, 1H,
3a-H, J 11.1, 6.0 and 13.3 Hz), 4.25 (dd, 1H, 4-HA, J –11.3 and 10.9 Hz),
4.61 (dd, 1H, 4-HB, J –11.4 and 6.0 Hz), 4.82 (dd, 1H, 4-H, JCH–NH 13.5
and 5.0 Hz), 6.9–8.3 (m, 9H, ArH + NH).
84 Mendeleev Commun. 2005